Spore-forming Clostridium difficile-associated diseases (CDAD) remain an important nosocomial infection associated with significant morbidity and mortality. In recent years, the incidence of CDAD has unfortunately increased and high rates of recurrent disease continue with currently available treatment regimens. Typically, Clostridium difficile is transmitted by the fecal-oral route. Spores that persist in the environment survive the gastric acid barrier and germinate in the colon. Toxins released from vegetative C. difficile cells are responsible for clinical CDAD.
Vegetative C. difficile can only survive 15 minutes aerobically, but the bacteria are nonetheless very difficult to eradicate because they form spores. C. difficile spores can be found as airborne particles, attached to inanimate surfaces such as hard surfaces and fabrics, and attached to surfaces of living organisims, such as skin and hair. Spores can be found on a patient's skin as well as on any surface in the room that the infected patient occupied. During exams these spores can be transferred to the hands and body of healthcare workers and thereby spread to subsequent equipment and areas they contact.
Hospital discharges for CDAD in the United States doubled between 1996 and 2003. These nosocomial infections are extremely costly to hospitals at $1.28 to $9.55 billion annually in the U.S. alone, mostly due to infected patients requiring extended stays of 3.6 to 14.4 days. Complications of CDAD include life-threatening diarrhea, pseudo-membranous colitis, toxic megacolon, sepsis, and death. Expenses related to treatment of these conditions ranges from $3,669 to $27,290 per patient. CDAD causes death in 1-2% of affected patients.
People are most often infected in hospitals, nursing homes, or institutions, although C. difficile infection in the community, outpatient setting is increasing. C. difficile infection (CDI) can range in severity from asymptomatic to severe and life-threatening, especially among the elderly. The rate of C. difficile acquisition is estimated to be 13% in patients with hospital stays of up to 2 weeks, and 50% in those with hospital stays longer than 4 weeks.
While currently available antibiotics used for treatment of recurrent CDAD lead to symptomatic improvement, they are essentially ineffective against C. difficile spores, the transmissible form of the disease. This causes a high risk of relapse occurring post-therapy as sporulated microorganisms begin to germinate. Therefore, controlling C. difficile infection requires limiting the spread of spores by good hygiene practices, isolation and barrier precautions, and environmental cleaning.
Because of the prevalence of C. difficile in hospitals, healthcare workers and researchers have an interest in developing an agent that can kill C. difficile and its spores.